Infectious pathogens including bacteria, mycobacteria, fungi, viruses and protozoa are known to cause a wide variety of recognizable ocular infections that can be diagnosed clinically and treated with specific antibiotic therapy. Typically infectious ocular diseases are characterized by an inflammatory response to rid the host of the offending microorganism. There are several ocular conditions including neoplastic, degenerative and autoimmune diseases in which routine clinical investigations reveal no direct evidence of a causative infectious pathogen. Our group is interested in investigating the role of infectious pathogens in the pathogenesis of ocular diseases that may lead to better diagnostic methods and treatment strategies. In ongoing clinical studies in our group continue to investigate role of the Human T cell Lymphotrophic Virus, Type 1 (HTLV-1) in the pathogenesis of human ocular disease by following a cohort of HTLV-1 infected patients predominantly of African heritage with adult T-cell leukemia/lymphoma (ATL) and HTLV-1 associated myelopathy/Tropical spastic paraparesis (HAM/TSP). Our evaluations of this group of patients suggest that genetic and environmental factors may influence the ophthalmic manifestations of HTLV-1 as the clinical findings seem to differ significantly from the ocular finding known to occur in Japanese populations endemic for the HTLV-1 infection. Over the past year a new clinical entity, the severe acute respiratory syndrome (SARS), was found to be caused by a coronavirus. Although the primary clinical manifestation of SARS is pulmonary, ocular complaints have been reported in affected patients. We had an opportunity to evaluate 9 eyes of 8 patients with SARS postmortem. Histopathologic examination revealed mild cyclitis in one pair of eyes and small optic hemorrhage in one eye but no evidence of a viral infection could be demonstrated by light or electron microscopy. Because retinal degeneration could be induced by a coronavirus in an animal model, a clinical protocol has been proposed to determine if the SARS agent, a coronavirus, may induce retinal changes in affected patients. Helicobacter pylori is a gram negative bacteria which has been associated with gastritis, gastric and duodenal ulcers, gastric adenocarcinoma and gastric mucosa associated lymphoid tissue (MALT) lymphoma. Reports have implicated H. pylori in the pathogenesis of ocular disease including glaucoma and ocular rosacea. Recently we have identified H. pylori genes in the conjunctiva of 6/7 patients with conjunctival MALT lymphoma suggesting a direct role for the bacteria in the development of this extra-intestinal malignancy. Presently, we are formulating seroepidemiologic studies to investigate a possible role for H. pylori in patients with uveitis and ocular surface disease. Finally, we have also demonstrated the presence of Histoplasma capsulatum DNA in a fixed ocular tissue specimen of a patient with choroidal inflammatory infiltrates confirming the clinical suspicion of ocular histoplasmosis which would have otherwise not been diagnosed definitively. These findings offer the potential for the development of better diagnostic tools and treatments of ocular disease related to infectious agents.